This training program is designed to provide intensive laboratory training for M.D., M.D./Ph.D. as well as for Ph.D. post-doctoral fellows. The primary emphasis in the competitive renewal application will be in training physician scientists to be successful in translational biomedical laboratory research in hematology and oncology. In addition to an ongoing focus on disorders affecting the hematopoietic system, such as (1) hemoglobinopathies, and thalassemia, (2) cell biology and signal transduction and differentiation of hematopoietic cells, (3) malignancies affecting the hematopoietic and other systems, and (4) gene therapy, two new research themes, chemical biology and hematopoietic stem cells, complement these other themes. They reflect the addition of new faculty that includes Professors Carolyn Bertozzi, Michael Marletta, and James Wells, chemistry faculty, and Emmanuelle Passague in Stem Cells. In addition to training in molecular and cell biology, signal transduction, and cell differentiation, trainees will be exposed to new chemical approaches to characterizing cell surface glyosylated membrane proteins and lipids, recombinant proteins for oxygen delivery, and stem cells for the study of normal and abnormal hematopoiesis. New Training Grant faculty who will enhance the cell biology and signal transduction theme include Cynthia Kenyon who has made major discoveries in the IGF signaling pathway and in relating this pathway to aging. Our primary goal is to equip physician scientists with basic biomedical research skills that will enable them to sustain this focus after completion of training by providing opportunities in laboratories of highly successful scientists who are committed to translational research. In turn, the faculty have made a substantial commitment to training physician scientists. We will continue to recruit candidates with significant translational interest and motivation into our training program. By enrolling in an intensive laboratory research training program, trainees will extend their knowledge base and learn new research tools. We believe that the retention rate of these trainees in research will be increased significantly by the addition of the new training faculty as well as retention of many of the previous faculty.